10-29683621-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001323599.2(SVIL):​c.-301+2932T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 152,082 control chromosomes in the GnomAD database, including 8,983 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.34 ( 8983 hom., cov: 32)

Consequence

SVIL
NM_001323599.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.42
Variant links:
Genes affected
SVIL (HGNC:11480): (supervillin) This gene encodes a bipartite protein with distinct amino- and carboxy-terminal domains. The amino-terminus contains nuclear localization signals and the carboxy-terminus contains numerous consecutive sequences with extensive similarity to proteins in the gelsolin family of actin-binding proteins, which cap, nucleate, and/or sever actin filaments. The gene product is tightly associated with both actin filaments and plasma membranes, suggesting a role as a high-affinity link between the actin cytoskeleton and the membrane. The encoded protein appears to aid in both myosin II assembly during cell spreading and disassembly of focal adhesions. Several transcript variants encoding different isoforms of supervillin have been described. [provided by RefSeq, Apr 2016]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SVILNM_001323599.2 linkc.-301+2932T>C intron_variant Intron 2 of 38 NP_001310528.1 A0A6I8PIX7
SVILNM_001323600.1 linkc.-301+2932T>C intron_variant Intron 2 of 36 NP_001310529.1
SVILNM_003174.3 linkc.-301+2932T>C intron_variant Intron 2 of 35 NP_003165.2 O95425-2Q569J5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SVILENST00000375400.7 linkc.-301+2932T>C intron_variant Intron 2 of 35 1 ENSP00000364549.3 O95425-2
SVILENST00000674475.1 linkc.-301+2932T>C intron_variant Intron 2 of 38 ENSP00000501521.1 A0A6I8PIX7
SVILENST00000674490.1 linkc.-301+2932T>C intron_variant Intron 2 of 5 ENSP00000501398.1

Frequencies

GnomAD3 genomes
AF:
0.340
AC:
51714
AN:
151964
Hom.:
8973
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.392
Gnomad AMI
AF:
0.216
Gnomad AMR
AF:
0.307
Gnomad ASJ
AF:
0.251
Gnomad EAS
AF:
0.431
Gnomad SAS
AF:
0.350
Gnomad FIN
AF:
0.340
Gnomad MID
AF:
0.332
Gnomad NFE
AF:
0.316
Gnomad OTH
AF:
0.320
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.340
AC:
51765
AN:
152082
Hom.:
8983
Cov.:
32
AF XY:
0.343
AC XY:
25519
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.392
Gnomad4 AMR
AF:
0.307
Gnomad4 ASJ
AF:
0.251
Gnomad4 EAS
AF:
0.432
Gnomad4 SAS
AF:
0.351
Gnomad4 FIN
AF:
0.340
Gnomad4 NFE
AF:
0.316
Gnomad4 OTH
AF:
0.323
Alfa
AF:
0.319
Hom.:
10803
Bravo
AF:
0.342
Asia WGS
AF:
0.418
AC:
1455
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
8.2
DANN
Benign
0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs11007696; hg19: chr10-29972550; API